Identification and characterisation of the currently unknown gene for human carnosine synthetase (EC 6.3.2.11) upon purification of the homologous enzyme from Gallus gallus

目前未知的人肌肽合成酶基因（EC 6.3.2.11）将被确定，以促进糖尿病肾病发展中肌肽代谢的研究。此外，人体骨骼肌中高浓度（高达20毫米）的二肽肌肽（β-丙烯酰- l-组氨酸）的生理作用仍不清楚。肌肽产生酶的生化特性有助于对肌肽功能的全面了解。我们最近发现，肌肽降解酶血清肌肽酶的一种变体与糖尿病肾病的保护有关。这种效应的生物学基础尚不清楚。肌肽合成酶较早从鸡中纯化出来，但没有得到序列信息。据报道，这种酶很难处理。用新的色谱方法分离蛋白质应该很简单。纯化后，将生成序列信息，并在计算机上识别同源哺乳动物基因。观察其在不同组织中的表达水平。肌肽合成酶在糖尿病肾病发病机制中可能的功能变异的相关性将通过患者和对照组的关联研究进行检验。

The currently unknown gene for human carnosine synthetase (EC 6.3.2.11) will be identified in order to facilitate studies on carnosine metabolism in the development of diabetic nephropathy. Furthermore, the physiological role of the dipeptide carnosine (β-alanyl-L-histidine), which is present in high concentrations (up to 20 mM) in human skeletal muscle, is still unclear. The biochemical characterization of the carnosine producing enzyme should contribute to the general understanding of carnosine function. We recently found that a variant of the carnosin-degrading enzyme serum carnosinase is associated with protection from diabetic nephrophathy. The biological basis of this effect is unclear. Carnosine synthetase has been purified earlier from Gallus gallus but sequence information was not produced. The enzyme was reported to be difficult to handle. With new chromatographic methods isolation of the protein should be straightforward. Following purification, sequence information will be generated and the homologous mammalian genes will be identified in silico. The expression level will be followed in various tissues. The relevance of possible functional variants of carnosine synthetase in the pathogenesis of diabetic nephropathy will be examined through association studies in patients and controls.